GHB receptor

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G protein-coupled receptor 172A
Identifiers
Symbol GPR172A
Entrez 79581
HUGO 30224
OMIM 607882
RefSeq NM_024531
UniProt Q9HAB3
Other data
Locus Chr. 8 q24.3

Gamma-hydroxybutyrate receptor or GHB receptor (GHBR or GHBr), originally identified as GPR172A, is a G protein-coupled receptor that binds gamma-Hydroxybutyric acid (GHB).

History[edit]

The existence of a specific GHB receptor was predicted by observing the action of GHB and related compounds that primarily act on GABAB receptors, but also exhibit a range of effects which were found not to be produced by GABAB activity, and so were suspected of being produced by a novel and at the time unidentified receptor target. Following the discovery of the "orphan" G-protein coupled receptor GPR172A, it was subsequently found to be the GHB receptor whose existence had been previously predicted.[1] The rat GHB receptor was first cloned and characterised in 2003[2] followed by the human receptor in 2007.[3]

Function[edit]

The function of the GHB receptor appears to be quite different from that of the GABAB receptor. It shares no sequence homology with GABAB, and administration of mixed GHBR/GABAB agonists along with a selective GABAB antagonist or selective agonists for the GHB receptor which are not agonists at GABAB, do not produce a sedative effect, instead causing a stimulant effect followed by convulsions at higher doses, thought to be mediated through increased Na+/K+ current and increased release of dopamine and glutamate.[4][5][6][7][8][9]

Selective Ligands[edit]

  • (R)-4-[4′-(2-iodobenzyloxy)phenyl]-GHB[10]

Agonists[edit]

Antagonists[edit]

References[edit]

  1. ^ Snead OC (November 2000). "Evidence for a G protein-coupled gamma-hydroxybutyric acid receptor". J. Neurochem. 75 (5): 1986–96. doi:10.1046/j.1471-4159.2000.0751986.x. PMID 11032888. 
  2. ^ Andriamampandry C, Taleb O, Viry S, et al. (September 2003). "Cloning and characterization of a rat brain receptor that binds the endogenous neuromodulator gamma-hydroxybutyrate (GHB)". FASEB J. 17 (12): 1691–3. doi:10.1096/fj.02-0846fje. PMID 12958178. 
  3. ^ Andriamampandry C, Taleb O, Kemmel V, Humbert JP, Aunis D, Maitre M (March 2007). "Cloning and functional characterization of a gamma-hydroxybutyrate receptor identified in the human brain". FASEB J. 21 (3): 885–95. doi:10.1096/fj.06-6509com. PMID 17197387. 
  4. ^ Cash, C; Gobaille, S; Kemmel, V; Andriamampandry, C; Maitre, M (1999). "γ-hydroxybutyrate receptor function studied by the modulation of nitric oxide synthase activity in rat frontal cortex punches". Biochemical Pharmacology 58 (11): 1815–9. doi:10.1016/S0006-2952(99)00265-8. PMID 10571257. 
  5. ^ Maitre M, Humbert JP, Kemmel V, Aunis D, Andriamampandry C (March 2005). "[A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse]" [A mechanism for gamma-hydroxybutyrate (GHB) as a drug and a substance of abuse]. Med Sci (Paris) (in French) 21 (3): 284–9. doi:10.1051/medsci/2005213284. PMID 15745703. 
  6. ^ Castelli MP, Ferraro L, Mocci I, et al. (November 2003). "Selective gamma-hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of gamma-hydroxybutyric acid". J. Neurochem. 87 (3): 722–32. doi:10.1046/j.1471-4159.2003.02037.x. PMID 14535954. 
  7. ^ Castelli MP (November 2008). "Multi-faceted aspects of gamma-hydroxybutyric Acid: a neurotransmitter, therapeutic agent and drug of abuse". Mini Rev Med Chem 8 (12): 1188–202. doi:10.2174/138955708786141025. PMID 18855733. 
  8. ^ Crunelli V, Emri Z, Leresche N (February 2006). "Unravelling the brain targets of γ-hydroxybutyric acid". Curr Opin Pharmacol 6 (1): 44–52. doi:10.1016/j.coph.2005.10.001. PMC 2174623. PMID 16368267. 
  9. ^ Carter LP, Koek W, France CP (October 2008). "Behavioral Analyses of GHB: Receptor Mechanisms". Pharmacol. Ther. 121 (1): 100–14. doi:10.1016/j.pharmthera.2008.10.003. PMC 2631377. PMID 19010351. 
  10. ^ Høg S, Wellendorph P, Nielsen B, et al. (2008). "Novel High-Affinity and Selective Biaromatic 4-Substituted gamma-Hydroxybutyric Acid (GHB) Analogues as GHB Ligands: Design, Synthesis, and Binding Studies". J. Med. Chem. 51 (24): 8088–95. doi:10.1021/jm801112u. PMID 19053823. 
  11. ^ Ticku MK, Mehta AK (October 2008). "Characterization and pharmacology of the GHB receptor". Annals of the New York Academy of Sciences 1139: 374–85. doi:10.1196/annals.1432.048. PMID 18991884.